15-41710993-C-G

Variant names:

• chr15-41710993-C-G
• rs761227360
• NM_001400225.1:c.2728C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001400225.1(MGA):​c.2728C>G​(p.Arg910Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MGA NM_001400225.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968
• Publications: 0 publications found

Genes affected

MGA (HGNC:14010): (MAX dimerization protein MGA) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell fate specification and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Part of MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24893373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400225.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGA	NM_001400225.1	MANE Select	c.2728C>G	p.Arg910Gly	missense	Exon 8 of 24	NP_001387154.1	A0A994J6L2
	MGA	NM_001164273.2		c.2728C>G	p.Arg910Gly	missense	Exon 8 of 24	NP_001157745.1	Q8IWI9-4
	MGA	NM_001080541.3		c.2728C>G	p.Arg910Gly	missense	Exon 8 of 23	NP_001074010.2	Q8IWI9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGA	ENST00000703841.1	MANE Select	c.2728C>G	p.Arg910Gly	missense	Exon 8 of 24	ENSP00000515495.1	A0A994J6L2
	MGA	ENST00000566586.6	TSL:1	c.2728C>G	p.Arg910Gly	missense	Exon 8 of 23	ENSP00000456141.1	Q8IWI9-3
	MGA	ENST00000916432.1		c.2728C>G	p.Arg910Gly	missense	Exon 8 of 24	ENSP00000586491.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.97
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.82
MutPred		0.27		Loss of MoRF binding (P = 0.0156)
MVP		0.35
MPC		0.52
ClinPred		0.89	D
GERP RS		5.9
gMVP		0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761227360; hg19: chr15-42003191;